Animal Models of Ischemic Stroke with Different Forms of Middle Cerebral Artery Occlusion.

Ischemic stroke is a common type of stroke that significantly affects human well-being and quality of life. In order to further characterize the pathophysiology of ischemic stroke and develop new treatment strategies, ischemic stroke models with controllable and consistent response to potential clinical treatments are urgently needed. The middle cerebral artery occlusion (MCAO) model is currently the most widely used animal model of ischemic stroke. This review discusses various methods for constructing the MCAO model and compares their advantages and disadvantages in order to provide better approaches for studying ischemic stroke.

Integration of molecular pathology with histopathology to accurately evaluate the biological behaviour of WHO grade 2 meningiomas and patient prognosis.

PURPOSE: A molecular pathological grading method was tested in WHO grade 2 meningiomas to judge whether this molecular grading can more accurately evaluate meningioma biological behaviour. METHODS: The medical records and paraffin-embedded tissues of surgically resected WHO grade 2 meningioma patients in our department from January 1, 2010, to December 31, 2020, were collected. The molecular pathological risk grading suggested by Sahm et al. was adopted and the patients were graded as low, intermediate and high risk. Progression-free survival (PFS), malignant progression-free survival (MPFS) and overall survival (OS) were analysed. Univariate and multivariate analysis were performed to determine the relationship between molecular risk grading and patient survival. RESULTS: Of the 98 patients, 13 (13.2%) were graded as low risk, 63 patients (64.3%) were graded as intermediate risk, and 22 patients (22.4%) were graded as high risk. With increasing molecular risk grade, the rates of tumour recurrence, malignant progression and mortality increased significantly (P < 0.05). Multivariate analysis showed that molecular risk grading was negatively associated with PFS (HR 0.018, 95% CI 0.003-0.092), MPFS (HR 0.040, 95% CI 0.006-0.266) and OS (HR 0.088, 95% CI 0.016-0.472) (P < 0.01), and gross total resection (Simpson grade I-III) significantly prolonged PFS (HR 5.882, 95% CI 2.538-13.699) and OS (HR 2.611, 95% CI 1.117-7.299) (P < 0.05). CONCLUSION: Sahm et al.'s molecular risk grading can further refine the classification of WHO grade 2 meningiomas and more accurately evaluate their biological behaviour and patient prognosis.

Treatment Outcomes and Risk Factors of Multidrug-Resistant Tuberculosis Patients in Xi'an China, a Retrospective Cohort Study.

Background: Long-term regimens are widely used for multidrug-resistant tuberculosis (MDR-TB) in North-West China; however, risk factors associated with the treatment outcomes are not well known. Methods: This was a retrospective cohort study of MDR-TB patients treated with longer regimen in Xi'an from 2017 to 2019. Risk factors associated with the treatment outcome were analyzed using multiple logistic regression. Results: Of the 446 patients with MDR-TB included, 215 were cured, 84 completed treatment, 23 failed treatment, 108 were lost to follow-up, and 16 died. Unfavorable outcome risk factors were age >40 years (OR = 3.25, 95% CI = 2.12-4.98), male sex (OR = 2.53, 95% CI = 1.52-4.22), and re-treated tuberculosis (OR = 1.70, 95% CI = 1.11-2.61), whereas poor treatment outcome risk factors were age >40 years (OR = 5.51, 95% CI = 2.52-12.07), fluoroquinolones not used in the regimen (OR = 3.31, 95% CI = 1.45-7.51), and smear-positive (OR = 4.0, 95% CI = 1.47-10.8). Conclusion: In Xi'an, MDR-TB treatments with long-term regimens had low success rates, and age, sex, and tuberculosis treatment history were risk factors of MDR-TB treatment outcomes.

Modified Valsalva maneuver after burr-hole drainage of chronic subdural hematomas: A single-center cohort study.

Background: Previous studies on the management of chronic subdural hematoma (cSDH) mainly focused on the risk of postoperative recurrence and measures to prevent it. In this study, we propose the use of a non-invasive postoperative treatment method, the modified Valsalva maneuver (MVM), as a means of reducing the recurrence of cSDH. This study aims to clarify the effects of MVM on functional outcomes and recurrence rates. Methods: A prospective study was conducted at the Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from November 2016 to December 2020. The study included 285 adult patients who underwent burr-hole drainage for the treatment of cSDH and received subdural drains. These patients were divided into two groups: the MVM group (n = 117) and the control group (n = 98). In the MVM group, patients received treatment with a customized MVM device for at least 10 times per hour, 12 h per day. The study's primary endpoint was the recurrence rate of SDH, while functional outcomes and morbidity 3 months after surgery were the secondary outcomes. Results: In the current study, 9 out of 117 patients (7.7%) in the MVM group experienced a recurrence of SDH, while 19 out of 98 patients (19.4%, p < 0.05) in the HC group experienced a recurrence of SDH. Additionally, the infection rate of diseases such as pneumonia (1.7%) was significantly lower in the MVM group compared to the HC group (9.2%, p < 0.001, odds ratio (OR = 0.1). After 3 months of the surgery, 109 out of 117 patients (93.2%) in the MVM group achieved a favorable prognosis, compared to 80 out of 98 patients (81.6%) in the HC group (p = 0.008, with an OR of 2.9). Additionally, infection rate (with an OR of 0.2) and age (with an OR of 0.9) are independent predictors of a favorable prognosis at the follow-up stage. Conclusions: The use of MVM in the postoperative management of cSDHs has been shown to be safe and effective, resulting in reduced rates of cSDH recurrence and infection following burr-hole drainage. These findings suggest that MVM treatment may lead to a more favorable prognosis at the follow-up stage.

Myoglobin Offers Higher Accuracy Than Other Cardiac-Specific Biomarkers for the Prognosis of COVID-19.

Although sporadic studies have shown that myoglobin may have better prognostic performance than other cardiac markers in COVID-19, a comprehensive comparative study is lacking. Herein, we retrospectively analyzed the clinical and laboratory data of COVID-19 patients admitted to the Guanggu Campus of Wuhan Tongji Hospital from February 9, 2020 to March 30, 2020, intending to compare the prognostic accuracy of three commonly used cardiac markers on COVID-19 mortality. Our results revealed that abnormal increases in myocardial biomarkers were associated with a significantly increased risk of in-hospital mortality with COVID-19. Interestingly, myoglobin, a non-cardiac-specific biomarker, also expressed in skeletal myocytes, had even higher prognostic accuracy than cardiac-specific biomarkers such as high-sensitivity troponin I (hs-TnI) and creatine kinase-MB (CK-MB). More importantly, multivariate Cox analysis showed that myoglobin, rather than hs-TnI or CK-MB, was independently prognostic for in-hospital mortality in COVID-19. These results were further confirmed by subgroup analyses of patients with severe and critical illnesses and those without a history of cardiovascular disease. Our findings suggest that myoglobin may be a reliable marker of illness reflecting general physiological disturbance and help to assess prognosis and treatment response in patients with COVID-19.

A survival analysis of surgically treated incidental low-grade glioma patients.

To evaluate the surgical effect on survival in patients with incidental low-grade glioma (LGG) through comparison between asymptomatic and symptomatic patients. The medical records of surgically treated adult cerebral incidental LGG (iLGG) patients in our department between January 2008 and December 2015 were retrospectively reviewed. The survival of patients was calculated starting from the initial imaging diagnosis. Factors related to progression-free survival (PFS), overall survival (OS) and malignant progression-free survival (MPFS) were statistically analyzed. Seventy-five iLGG patients underwent surgery: 49 in the asymptomatic group, who underwent surgery in the asymptomatic period, and 26 in the symptomatic group, who underwent surgery after the tumor had grown and the patients had developed tumor-related symptoms. Significantly more tumors were initially located adjacent to the functional area in the symptomatic group than in the asymptomatic group (P < 0.05), but there was no significant difference in the total resection rate between the two groups. The incidence of postoperative complications (15.4%) and postoperative epilepsy (23.1%) was higher in the symptomatic group than in the asymptomatic group (4.1% and 10.2%, respectively). Multivariate analysis showed that surgical timing, namely, surgery performed before or after symptom occurrence, had no significant effect on PFS, OS or MPFS, while total resection significantly prolonged PFS, OS and MPFS, and the pathology of oligodendroglioma was positively correlated with PFS and OS (P < 0.05). Surgical timing for iLGGs should facilitate total resection. If total resection can be achieved, even after symptom occurrence, patients can achieve comparable survival benefits to those treated with surgery in the asymptomatic phase.

Inflammation-associated factors for predicting in-hospital mortality in patients with COVID-19.

The aim is to explore the relation between inflammation-associated factors and in-hospital mortality and investigate which factor is an independent predictor of in-hospital death in patients with coronavirus disease-2019. This study included patients with coronavirus disease-2019, who were hospitalized between February 9, 2020, and March 30, 2020. Univariate Cox regression analysis and least absolute shrinkage and selection operator regression (LASSO) were used to select variables. Multivariate Cox regression analysis was applied to identify independent risk factors in coronavirus disease-2019. A total of 1135 patients were analyzed during the study period. A total of 35 variables were considered to be risk factors after the univariate regression analysis of the clinical characteristics and laboratory parameters (p < .05), and LASSO regression analysis screened out seven risk factors for further study. The six independent risk factors revealed by multivariate Cox regression were myoglobin (HR, 5.353; 95% CI, 2.633-10.882; p < .001), C-reactive protein (HR, 2.063; 95% CI, 1.036-4.109; p = .039), neutrophil count (HR, 2.015; 95% CI, 1.154-3.518; p = .014), interleukin 6 (Il-6; HR, 9.753; 95% CI, 2.952-32.218; p < .001), age (HR, 2.016; 95% CI, 1.077-3.773; p = .028), and international normalized ratio (HR, 2.595; 95% CI, 1.412-4.769; p = .002). Our results suggested that inflammation-associated factors were significantly associated with in-hospital mortality in coronavirus disease-2019 patients. C-reactive protein, neutrophil count, and interleukin 6 were independent factors for predicting in-hospital mortality and had a better independent predictive ability. We believe these findings may allow early identification of the patients at high risk for death, and can also assist in better management of these patients.

Cardiac Biomarker Levels and Their Prognostic Values in COVID-19 Patients With or Without Concomitant Cardiac Disease.

The coronavirus disease 2019 (COVID-19) pandemic has become a global threat. Increases in cardiac biomarkers are common and are associated with adverse outcomes in patients with COVID-19. Although these increases are more likely to occur in cases with concomitant cardiac disease, the differences in cardiac biomarker levels between patients with and without cardiac disease and their associations with in-hospital mortality are largely unknown. A consecutive serial of laboratory-confirmed COVID-19 cases was retrospectively enrolled. Clinical characteristics, laboratory results, and outcome data were collected. The levels of cardiac biomarkers were evaluated and compared by stratifying patients according to concomitant cardiac conditions and clinical classifications. The prognostic efficacy of cardiac biomarker levels on admission was also assessed. Among the overall study population and survived patients, the cardiac biomarker levels at both the early and late stages in cardiac patients were significantly higher than those in non-cardiac patients. However, their concentrations in cardiac patients were comparable to non-cardiac ones among non-survivors. The cardiac biomarker levels at the late stage of the disease were significantly decreased compared to those at the early stage among patients who were alive. Whereas, the late-stage biomarker levels were significantly increased in patients who ultimately died. Subgroup analysis illustrated that increases in cardiac biomarkers were closely related to the severity of the disease, and were prognostic for high risks of in-hospital mortality in non-cardiac, rather than in cardiac patients. Myo and NT-proBNP, rather than Hs-TnI and CK-MB, were independently associated with in-hospital mortality in the overall population and non-cardiac patients. However, these associations were not significant among cardiac patients. In conclusion, our results helped better understand the release pattern and prognostic performance of cardiac biomarkers in patients with COVID-19. Increased levels of Myo and NT-proBNP on admission could be useful markers for early identifying high-risk patients. However, special attention must be paid when implementing the prognostic function for cardiac patients.

Analyses of prognosis-related factors of intracranial solitary fibrous tumors and hemangiopericytomas help understand the relationship between the two sorts of tumors.

Increasing evidence has suggested a close relationship between solitary fibrous tumors (SFTs) and hemangiopericytomas (HPCs) in the central nervous system (CNS). However, CNS SFTs differentiate from HPCs in their clinical behavior and patient prognoses. Analyses of prognosis-related factors can help clarify the relationship between SFT and HPC. The intracranial SFT and HPC cases treated in our departments from January 2002 to December 2012 were retrospectively reviewed. The SFT and HPC cases were also combined into an SFT/HPC group. The factors associated with patient progression-free survival (PFS) and overall survival (OS) were statistically analyzed using uni- and multivariate analyses. Fifty-eight intracranial SFT/HPC patients including 38 SFT patients and 20 HPC patients were treated during this period. The "Marseille grading" evaluated upon the histological aggressive phenotypes was applied in this study. The grading reflected a malignant progression ranging from "conventional" SFTs (grade I) to WHO III HPCs (grade III), and grade was negatively correlated with the PFS and OS of the SFT, HPC and SFT/HPC patients (P < 0.05).The multivariate analyses revealed that gross total resection (GTR) was significantly positively correlated with PFS and OS in the SFT, HPC and SFT/HPC patients and that radiotherapy was significantly positively correlated with PFS in the HPC and SFT/HPC patients (P < 0.05). In conclusion, the intracranial SFTs and HPCs share common prognostic factors including extent of surgery and pathology, moreover, the histological grading of the aggressive phenotypes supports the unifying of the CNS SFT and HPC into one tumor entity of SFT/HPC.

Label-retaining assay enriches tumor-initiating cells in glioblastoma spheres cultivated in serum-free medium.

Label-retaining cells, which are characterized by dormancy or slow cycling, may be identified in a number of human normal and cancer tissues, and these cells demonstrate stem cell potential. In glioblastoma, label-retaining assays to enrich glioma stem cells remain to be fully investigated. In the present study, glioblastoma sphere cells cultured in serum-free medium were initially stained with the cell membrane fluorescent marker DiI. The fluorescence intensity during cell proliferation and sphere reformation was observed. At 2 weeks, the DiI-retaining cells were screened by fluorescence-activated cell sorting and compared phenotypically with the DiI-negative cells in terms of in vitro proliferation, clonogenicity and multipotency and for in vivo tumorigenicity, as well as sensitivity to irradiation and temozolomide treatment. It was observed that DiI-retaining cells accounted for a small proportion, <10%, within the glioblastoma spheres and that DiI-retaining cells proliferated significantly more slowly compared with DiI-negative cells (P=0.011, P=0.035 and P=0.023 in the of NCH421k, NCH441 and NCH644 glioblastoma sphere cell lines). Significantly increased clonogenicity (P=0.002, P=0.034 and P=0.016 in the NCH441, NCH644 and NCH421k glioblastoma sphere cell lines) and three-lineage multipotency were observed in DiI-retaining cells in vitro compared with DiI-negative cells. As few as 100 DiI-retaining cells were able to effectively generate tumors in the immunocompromised mouse brain, whereas the same number of DiI-negative cells possessed no such ability, indicating the increased tumorigenicity of DiI-retaining cells compared with DiI-negative cells. Furthermore, DiI-retaining cells demonstrated significant resistance following irradiation (P=0.012, P=0.024 and P=0.036) and temozolomide (P=0.003, P=0.005 and P=0.029) compared with DiI-negative cells in the NCH421k, NCH441 and NCH644 glioblastoma sphere cell lines, respectively. It was concluded that label-retaining cells in glioblastoma spheres manifest clear stem cell features and that the label-retaining assay may be utilized to further enrich glioma stem cells cultured under serum-free conditions for additional study.

Will an Asymptomatic Meningioma Grow or Not Grow? A Meta-analysis.

BACKGROUND: The treatment strategy for patients with an asymptomatic meningioma is still controversial. Key to an optimal decision is a careful evaluation of the growth possibilities of the meningioma by taking the patient's clinicoradiologic factors into consideration. However, previous studies have disagreed about the risk factors relating to tumor growth. METHODS: A comprehensive search of PubMed, Embase, and the ISI Web of Knowledge was performed. Using a meta-analysis with nine subsidiary studies including 777 patients, we analyzed the correlation of the growth pattern of meningioma with patient gender, tumor location, tumor calcification, magnetic resonance imaging (MRI) T2 signal intensity, and peritumoral brain edema. RESULTS: The growth rate of meningioma was negatively correlated with tumor calcification (odds ratio [OR]: 0.23; 95% confidence interval (CI), 0.11-0.46; p < 0.001) but positively associated with MRI T2 signal intensity (OR: 2.75; 95% CI, 1.75-4.33; p < 0.001). No correlations were found between tumor growth and other factors such as gender (OR: 1.29; 95% CI, 0.84-1.99; p = 0.24), skull base location (OR: 0.80; 95% CI, 0.25-2.58; p = 0.70), and peritumoral brain edema (OR: 1.24; 95% CI, 0.29-5.27; p = 0.77). CONCLUSIONS: Two factors, tumor calcification and low MRI T2 signal intensity, indicate the possibility of a slow growth meningioma. In such cases of asymptomatic meningioma, a follow-up strategy can be preferentially considered.

Clinical characteristics of patients with asymptomatic intracranial meningiomas and results of their surgical management.

Surgery performed during the asymptomatic phase of meningioma remains controversial. The effects of surgery and the factors associated with postsurgical complications and patient prognosis were studied to optimize surgical decisions for clinicians who treat asymptomatic patients. The medical records of 513 patients with meningiomas (112 patients were asymptomatic) treated at our hospital from May 2007 to April 2012 were retrospectively reviewed. The results were analyzed with univariate and multivariate analyses. Asymptomatic meningiomas were characterized by a more common cerebral hemispheric location, a smaller size, and a lack of peritumoral edema. A significantly higher Simpson I resection rate of 95.2 % was achieved in tumors located in the cerebral hemisphere; in contrast, a rate of 66.7 % was obtained in tumors located at the skull base (P = 0.003). The overall postsurgical complication rate was 13.6 %, which was lower than the rate of 21.7 % in the symptomatic patients. Hemiplegia was the most common complication, which occurred most often in the patients with tumors in parietal locations (P = 0.015). Ninety-two percent of the asymptomatic patients achieved a Glasgow Outcome Scale (GOS) score of 5 1 year after the operation, and significantly more patients younger than 60 years of age obtained a GOS score of 5 compared with patients older than 60 years of age (P = 0.006). To achieve maximal tumor resection and good patient recovery, tumor location and patient age should be carefully considered prior to choosing to perform surgery in asymptomatic patients.

Knockdown of checkpoint kinase 1 is associated with the increased radiosensitivity of glioblastoma stem-like cells.

Glioblastoma multiforme is an aggressive brain tumor with a poor prognosis. The glioblastoma stem-like cells (GSCs) represent a rare fraction of human glioblastoma cells with the capacity for multi-lineage differentiation, self-renewal and exact recapitulation of the original tumor. Interestingly, GSCs are more radioresistant compared with other tumor cells. In addition, the remarkable radioresistance of GSCs has been known to promote radiotherapy failure and therefore is associated with a significantly higher risk of a local tumor recurrence. Moreover, the hyperactive cell cycle checkpoint kinase (Chk) 1 and 2 play a pivotal role in the DNA damage response including radiation and chemical therapy. Based on aforementioned, we hypothesized that knockdown of Chk1 or Chk2 might confer radiosensitivity on GSCs and thereby increases the efficiency of radiotherapy. In this study, we knocked down the expression of Chk1 or Chk2 in human GSCs using lentivirus-delivered short hairpin RNA (shRNA) to examine its effect on the radiosensitivity. After radiation, the apoptosis rate and the cell cycle of GSCs were measured with Flow Cytometry. Compared with control GSCs (apoptosis, 7.82 ± 0.38%; G2/M arrest, 60.20 ± 1.28%), Chk1 knockdown in GSCs increased the apoptosis rate (37.87 ± 0.32%) and decreased the degree of the G2/M arrest (22.37 ± 2.01%). In contrast, the radiosensitivity was not enhanced by Chk2 knockdown in GSCs. These results suggest that depletion of Chk1 may improve the radio-sensitivity of GSCs via inducing cell apoptosis. In summary, the therapy targeting Chk1 gene in the GSCs may be a novel way to treat glioblastoma.

Expression and regulation of AC133 and CD133 in glioblastoma.

The biological significance of CD133 in glioblastoma is controversial. Above all, there is disagreement concerning the proper approach, the appropriate (cell) model and the suitable microenvironment to study this molecule, often leading to inconsistent experimental results among studies. In consideration of a primary need to dissect and to understand the CD133 phenotype in glioblastoma we performed a comprehensive analysis of CD133 expression and regulation in a large set of glioblastoma cell lines (n = 20) as well as in tumor xenografts. Our analysis considered alternatively spliced mRNA transcripts, different protein epitopes as well as varying sub-cellular localizations of CD133 and explored its regulation under pertinent micro-environmental conditions. CD133 mRNA and CD133 protein could be detected in all relevant types of glioblastoma cell lines. In addition, we detected frequent intracellular CD133 protein accumulations located to the ER and/or Golgi apparatus but seemingly unrelated to particular CD133 splice variants or protein epitopes. In contrast, membrane-bound expression of CD133 was restricted to tumor cells bearing the extracellular CD133 epitope AC133. Only in these cells, differentiation and oxygen levels clearly impacted on AC133 expression and to some extent also influenced CD133 mRNA and protein expression. Most importantly, however, modulation of AC133 levels could occur independently of changes in CD133 mRNA transcription, CD133 protein translation, protein retention or protein shedding. Our results suggest that the AC133 epitope, rather than CD133 mRNA or protein, mirrors malignancy-related tumor traits such as tumor differentiation and local oxygen tension levels, and thus corroborate its role as a biologically relevant cancer marker.